The present invention relates generally to methods, apparatus and computer program products for measuring blood oxygen saturation in a vessel, such as a retinal vessel and, more particularly, to methods, apparatus and computer program products for processing images of a vessel, such as a retinal vessel, obtained with light of different wavelengths to obtain a more accurate measurement of the percent transmittance of the vessel at each wavelength and, in turn, a more accurate measurement of the blood oxygen saturation of the vessel.
A variety of spectroscopic oximetry techniques have been developed to monitor the blood oxygen saturation and blood oxygen content in vessels, such as retinal vessels. By monitoring the blood oxygen saturation, the arteriovenous oxygen difference can be determined as described by U.S. Pat. No. 5,308,919 to Thomas E. Minnich, U.S. Pat. No. 5,776,060 to Matthew H. Smith, et al., and U.S. Pat. No. 5,935,076 to Matthew H. Smith, et al. Based upon the arteriovenous oxygen difference, the cardiac output of a subject can be determined in order to assist in post-operative monitoring and the management of critically ill patients. By monitoring the blood oxygen saturation, the loss of blood can be detected, and the rate and quantity of blood loss over time can be estimated as described by U.S. Pat. No. 5,119,814 to Thomas E. Minnich.
In addition to the variety of invasive techniques that require blood to be drawn, oftentimes repeatedly, from a patient, a number of non-invasive spectroscopic oximetry techniques have been developed to measure the blood oxygen saturation of a patient without requiring blood to be drawn from the patient. For example, a number of non-invasive spectroscopic oximetry techniques have been developed which measure the blood oxygen saturation of a patient based upon the transmittance of the blood within a retinal vessel, such as a retinal vein or a retinal artery. For example, U.S. Pat. Nos. 5,776,060 and 5,935,076 describe techniques for measuring the oxygen saturation of blood within a retinal vessel by illuminating the retinal vessel with light having a combination of wavelengths and then measuring the transmittance of the blood within the retinal vessel in response to the illumination at each of the selected wavelengths. Based upon the respective transmittances of the blood within the retinal vessel that are measured at each of the selected wavelengths, the oxygen saturation of the blood within the retinal vessel can be determined. The contents of U.S. Pat. Nos. 5,776,060 and 5,935,076 are hereby incorporated by reference in their entirety.
While a retinal vessel can be illuminated with light of different wavelengths in a variety of manners, U.S. Pat. No. 6,244,712 which issued Jun. 12, 2001 to Matthew H. Smith, et al. describes an advantageous technique for alternately illuminating the posterior portion of an eye with the signals emitted by different lasers such that the resulting image has interlaced portions formed by signals returning from the posterior portion of the eye in response to illumination by different lasers. Since each laser is designed to emit signals having a different wavelength, the resulting image can therefore include data collected at each of a number of different wavelengths. The contents of U.S. Pat. No. 6,244,712 are also hereby incorporated by reference in their entirety.
While a retinal vessel can be illuminated by light having a variety of different wavelengths, at least one wavelength is generally in the red part of the spectrum. In this regard, the proper combination of wavelengths must be utilized in order to obtain data from which the transmittance of the blood and, in turn, the oxygen saturation of the blood within the retinal vessel can be determined. At least one of most any proper combination of wavelengths is typically in the red spectrum. Additionally, diode lasers are typically utilized as laser sources for illuminating a retinal vessel and a common wavelength of light emitted by a diode laser is in the red spectrum. Unfortunately, a retinal blood vessel absorbs light in the red spectrum relatively weakly compared to light having other wavelengths. As such, the signals in the red spectrum that are returning from the posterior portion of the eye will not exhibit as great a contrast between the retinal vessel and the underlying tissue bed, i.e., the background fundus, as signals having other wavelengths.
As described in U.S. patent application Ser. No. 10/134,360, the light with which a retinal vessel is illuminated may be reflected and transmitted in a variety of different manners. Of these different manners, single pass light that passes through the retinal vessel, diffuses laterally through the retinal and/or choroidal layers and then exits through the pupil without again traversing the retinal vessel contains the information relevant to determining the oxygen saturation of the blood in the retinal vessel. However, the other signals that have been reflected and transmitted in different manners contain information that is less useful and render the determination of the blood oxygen saturation more difficult. As such, an aperture may be disposed within the path of the optical signals returning from the eye in order to preferentially pass single pass optical signals while blocking optical signals that have been reflected and transmitted in other manners. While effective for preferentially passing single pass optical signals, the optical signals that pass through the aperture and are detected have a substantially lower intensity and contrast than the unfiltered optical signals returning from the posterior portion of the eye. U.S. patent application Ser. No. 10/134,360 was filed Apr. 29, 2002 by Matthew H. Smith, et al. and is incorporated herein in its entirety.
As a result of the reduced contrast exhibited by the optical signals having a wavelength in the red spectrum and the lower intensity and contrast of the single pass optical signals that are preferentially passed through the aperture, the resulting image may have a relatively low contrast and intensity, thereby rendering it difficult to distinguish the retinal vessel from the background fundus. This difficulty in distinguishing the retinal vessel from the background fundus is exacerbated since the coloration of the background fundus can vary significantly. As a result of the relatively low contrast between the retinal vessels and the background fundus, it is sometimes difficult to determine the percent transmittance of the retinal vessel and, in turn, the oxygen saturation of the blood within the retinal vessel with sufficient certainty.
Accordingly, it would be advantageous to develop improved methods and apparatus for determining the blood oxygen saturation within a vessel, such as a retinal vessel. In particular, it would be advantageous to develop improved methods and apparatus for evaluating the optical signals returning from the posterior portion of the eye in order to more reliably determine the percent transmittance of the retinal vessel in response to illumination by light of each of a number of different wavelengths and, in turn, to more precisely determine the blood oxygen saturation within the retinal vessel, especially in instances in which the resulting images have a relatively low contrast between the retinal vessel and the background fundus.
An improved method, apparatus and computer program product are therefore provided according to one aspect of the present invention for more accurately determining the percent transmittance of a vessel, such as a retinal vessel, at each of a number of different wavelengths and, in turn, for more accurately determining the blood oxygen saturation within the vessel. The method, apparatus and computer program product are particularly advantageous for determining the blood oxygen saturation within a retinal vessel from images having a relatively low contrast between the retinal vessel and a tissue bed, such as the background fundus, such as images resulting from the illumination of the retinal vessel with optical signals in the red spectrum and images that have been constructed from optical signals that have been filtered to preferentially pass single pass light. Methods are also provided according to other advantageous aspects of the present invention for generating background images of the tissue bed that underlies a vessel and for separating pixels representative of the tissue bed from pixels representative of a vessel.
According to one aspect, the method, apparatus and computer program product determine the blood oxygen saturation in a vessel based upon a plurality of images of the vessel that were obtained in response to illumination of the vessel with light of different wavelengths. In this regard, a plurality of background images are generated based upon respective images of the vessel. In order to generate the background images, an image of the tissue bed underlying the vessel is approximated from a respective image of the vessel. To generate the image of the tissue bed, the image of the vessel is processed to separate pixels representative of the vessel from pixels representative of the tissue bed. According to one aspect of the present invention, the pixels that formerly represented the vessel are then redefined based upon values of at least some of the pixels representative of the tissue bed, thereby creating the background image. In this regard, the pixels formerly representative of the vessel may be redefined by being scaled to have the same mean and standard deviation as the pixels representative of the tissue bed. Alternatively, the pixels formerly representative of the vessel may be redefined in accordance with curves that are fit based upon values of the pixels representative of the tissue bed that are on opposite sides of the vessel.
Thereafter, a plurality of transmittance images are determined based upon respective pairs of the background images and the images of the vessel. For example, each transmittance image can be determined by dividing the image of the vessel by the respective background image. Based upon the plurality of transmittance images, the blood oxygen saturation in the vessel may be determined. Additionally, an image of the blood oxygen saturation in the vessel may be generated.
A number of preliminary steps may be executed prior to generating the plurality of background images. In this regard, at least one vessel may be initially identified in each of the images of the vessel. The images of the vessel may then be registered or aligned with one another. As mentioned above, the plurality of images of the vessel may then be processed to separate pixels representative of the vessel from pixels representative of the tissue bed. While the images may be processed in various manners to separate pixels representative of the vessel from pixels representative of the tissue bed, the method of one advantageous aspect of the present invention examines the pixels of each image along lines extending across the vessel, such as in a direction perpendicular to the vessel. For each line of pixels, a threshold is determined based upon the values of the pixels along the line. For example, the threshold may be determined based upon at least one of a mean and a standard deviation of the values of the pixels along the respective line. In one embodiment, for example, the threshold x is determined as follows:
x={overscore (x)}xe2x88x92xcex1"sgr"x
wherein {overscore (x)} is the mean and "sgr"x is the standard deviation of the pixels along the respective line, and wherein xcex1 is a predefined constant. Once the threshold is determined, the pixels are separated along each line into pixels representative of the vessel and pixels representative of the tissue bed depending upon the relationship of the threshold for the respective line to values of the pixels along the line.
Even once the pixels representative of the vessel have been separated from the pixels representative of the tissue bed, the method, apparatus and computer program product may further process and clean up each image. Within each image, for example, pixels determined to be part of the vessel but that are at least partially surrounded by pixels representative of the tissue bed may be redefined to now also be representative of the tissue bed. The plurality of images may also be processed to identify a pixel in one image that differs from a corresponding pixel in another image in its representation of that portion of the image as either the vessel or the tissue bed. If any such pixels are identified, one of the pixels may be redefined to be consistent with the other pixel. Still further, the plurality of images may also be processed to identify a group of adjacent pixels that each represent the vessel and to redefine any pixels that are also initially representative of the vessel but are remote from the group of adjacent pixels to be representative of tissue bed.
Based upon these processing techniques, relatively clean images of the vessel can be generated which, in turn, can be utilized to generate background images and transmittance images and, in turn, to determine the blood oxygen saturation in the vessel in an accurate fashion. Moreover, as described above, the method, apparatus and computer program product are particularly advantageous for determining the blood oxygen saturation within a retinal vessel from images having a relatively low contrast between the retinal vessel and the background fundus, such as images resulting from the illumination of the retinal vessel with optical signals in the red spectrum and images that have been constructed from optical signals that have been filtered to preferentially pass single pass light.